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Herein, we report a case of rupture of nonfunctional adrenal adenoma treated by nonsurgical supportive management due to high risk for operation. A patient with end stage renal disease (ESRD) who was on hemodialysis visited our emergency room and complained of a sudden abdominal pain after a fall. A retroperitoneal hemorrhage with hematoma formation around the adrenal adenoma, which was caused by rupture of the adrenal adenoma, was detected by abdominal computed tomography (CT). Supportive management was performed, with serial CT follow-up instead of surgical adrenalectomy treatment because of high operative risk, due to hemodialysis. After 1 week, the patient’s vital signs stabilized and the patient did not further complain about abdominal symptoms. However, supportive embolization was performed and the size of hematoma was more decreased. We report a case of a patient on hemodialysis who experienced a rupture of a nonfunctioning adrenal adenoma, which was caused by low-energy trauma. The patient’s conditions improved with nonsurgical supportive management including embolization. Physicians should consider both surgical and nonsurgical management for the rupture of adrenal adenomas, depending on the patient situation. Therefore, nonsurgical supportive management such as embolization can be one therapeutic option for treating nonfunctioning adrenal adenoma rupture caused by low-energy trauma in a patient who has risks for operation due to combined comorbidities.

In this review, we consider the diverse risk factors in diabetes patients beyond hyperglycemia that are being recognized as contributors to diabetic peripheral neuropathy (DPN). Interest in such alternative mechanisms has been encouraged by the recognition that neuropathy occurs in subjects with metabolic syndrome and pre-diabetes and by the reporting of several large clinical studies that failed to show reduced prevalence of neuropathy after intensive glucose control in patients with type 2 diabetes. Animal models of obesity, dyslipidemia, hypertension, and other disorders common to both pre-diabetes and diabetes have been used to highlight a number of plausible pathogenic mechanisms that may either damage the nerve independent of hyperglycemia or augment the toxic potential of hyperglycemia. While pathogenic mechanisms stemming from hyperglycemia are likely to be significant contributors to DPN, future therapeutic strategies will require a more nuanced approach that considers a range of concurrent insults derived from the complex pathophysiology of diabetes beyond direct hyperglycemia.

Mean glucose values alone cannot explain the patterns of morbidity and mortality due to dysglycemia in diabetes. Development of continuous glucose monitoring systems has improved the analysis and interpretation of glycemic variability. The roles of glycemic components other than constant hyperglycemia in diabetic complications must be investigated because large clinical studies have indicated that risk factors besides the average glucose value of HbA1c are involved in chronic macrocomplications/microcomplications of diabetes. Among these complications, the pathogenesis of diabetic peripheral neuropathy is particularly complex, and several factors related to glucose and nonglucose pathways have been suggested as risk factors. There is little information regarding the effect of glycemic variability on diabetic peripheral neuropathy, unlike other microvascular complications of retinopathy and nephropathy, and whether glycemic variability causes harmful effects is still a matter of debate. In this review, we discuss the relationships between glycemic variability and diabetic peripheral neuropathy, focusing on somatosensory peripheral neuropathies rather than autonomic neuropathies.

Strict glucose control is a well-proven therapeutic approach for peripheral neuropathies in patients with diabetes. Alpha lipoic acid (ALA) has also been accepted as a therapeutic agent for diabetic peripheral neuropathy (DPN) in the respect of pathogenesis. However, the potential of ALA as a treatment for DPN in comparison to that of glucose control is unclear. In this study, we compared the neuroprotective potential of glucose control and ALA. Animals were divided into 6 groups based on the intervention used, as follows: normal, diabetes (DM), DM+racemic form of ALA, DM+R form of ALA, DM+once daily insulin glargine, and DM+once daily insulin glargine with twice daily insulin glulisine. Various sensory tests were performed after 12 weeks of treatment, and immunohistochemistry of nerve fibers obtained from the sciatic and cutaneous nerves was performed after 24 weeks of treatment. There were no significant differences between the ALA-treated and insulin-treated DM groups in the sensory tests or in antioxidant activity. The axonal diameters and myelin sheath area of the sciatic nerves and the cutaneous small nerves, as assessed based on intraepidermal nerve fiber density, were similar in the ALA-treated and insulin-treated animals, although there was a non-significant trend for a mild increase in the both basal and rapid-acting insulin group compared with non-treated DM group. In conclusion, our results suggest that the neuroprotective benefits of ALA and insulin-based glucose control may be similar, although glucose control may have had slightly more beneficial effects in this animal model of diabetes. Of note, glucose levels should be strictly controlled, including corrections for fluctuations in the glucose level, to obtain therapeutic benefits in DPN.

The exact effectiveness of supportive care activities, such as exercise, in diabetes patients has yet to be elucidated in the diabetic peripheral neuropathy (DPN) field. Therefore, this study was designed to investigate the effect of regular exercise on the peripheral nerves of streptozotocin-induced diabetic rats. The animals were divided as follows into six groups according to exercise combination and glucose control: Normal group, normal group with exercise (EXE), diabetic group (DM), DM group with EXE, DM + glucose control with insulin (INS), and DM + INS + EXE. Animals in the exercise groups were made to walk on a treadmill machine everyday for 30 min at a setting of 8 m/min without inclination. After 8 weeks, sensory parameters were evaluated, and after 16 weeks, biochemicals and peripheral nerves were quantified by immunohistochemistry and compared among experimental groups. The resulting data showed that fasting blood glucose levels and HbA1c levels were not influenced significantly by exercise in normal and DM groups. However, the current perception threshold and the von Frey stimulation test revealed higher thresholds in the DM + INS + EXE group than in the DM + INS group (P

Subacute painful thyroiditis occurs in association with viral infections [1, 2]. It has been proposed that many viruses are involved in its pathogenesis, and they include coxsackie, influenza, adenoviruses, and echoviruses. So far, however, no studies have reported the relationship between subacute painful thyroiditis and scrub typhus infection. We experienced two cases of subacute painful thyroiditis accompanied by scrub typhus infection. The first case is a 69-year-old woman who was admitted to the Department of Gastroenterology in Korea, in autumn. The patient had a 5-day history of myalgia, fever, sore throat, anterior neck pain, and diarrhea. The patient had a hobby of gardening. On history taking, eschar had peeled off several days ago. It is well known that Korea is an endemic area of scrub typhus. Considering her hobby, we checked anti-tsutsugamushi antibody titer by immunofixation assay (IFA). Total amount of antibody (IgM or IgG) to Orientia tsutsugamushi was in the ratio of 1:320. We also evaluated her neck pain. Laboratory findings showed free T4 69.2 pmol/L (normal range: 11.5–22.7), TSH 0.01 uU/mL (normal range: 0.35–5.50), and normal thyroid auto-antibodies (thyroid peroxidase, thyroglobulin, and TSH receptor). There were no antibodies against other viral infections. Neck ultrasound showed a multifocal hypoechoic area in the thyroid gland, accompanied by the decreased vascularity. Thyroid scan showed no increased uptake in both lobes. These findings are suggestive of scrub typhus infection and subacute thyroiditis. She was given doxycycline, b-blockers, and nonsteroidal antiinflammatory drugs (NSAIDs). After 2–3 weeks, she achieved an improvement in neck pain and generalized illness, and had a decrease in free T4 level to 27.6 pmol/L (Table 1). The second case is a 57-year-old woman who was admitted in autumn to the Department of Endocrinology in Korea with a chief complaint of a 7-day history of myalgia, fever, sore throat, neck pain, palpitation and decreased oral intake. She had tenderness in the both thyroid lobes, but had no eschar. Considering not only the fact that Korea is an endemic area but also the prevalence of scrub typhus is relatively higher during autumn, we measured anti-tsutsugamushi Ab titer by IFA, and it was 1:640. To evaluate the neck pain and palpitation, we examined the thyroid status. Laboratory findings showed free T4 122.5 pmol/L (normal range: 11.5–22.7), TSH 0.01 uU/mL (normal range: 0.35–5.50), and normal thyroid auto-antibodies. Neck ultrasound showed a mild inflammation of the thyroid, accompanied by the normal vascularity. Thyroid scan showed no increased uptake in both lobes. She was diagnosed with subacute thyroiditis accompanied by scrub typhus infection. She was given doxycycline, b-blockers, NSAIDs, and steroids (10 mg). After 2 weeks, she achieved an improvement in the symptoms, and had a decrease in free T4 level to 80.6 pmol/L (Table 1). On continuing the treatment with doxycycline for several days, anti-tsutsugamushi Ab titer fell to 1:160. Subacute painful thyroiditis is a transient inflammatory disease, and it is characterized by pain and tenderness of the thyroid gland. To our knowledge, our patients are the S. Kim T. S. Park H. S. Baek H. Y. Jin (&) Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Chonbuk National University Medical School, 634-18, Keum-Am Dong, Jeonju 561-712, South Korea e-mail: mdjinhy@jbnu.ac.kr

In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P < 0.05). The mean myelinated axonal area in the sciatic nerves was significantly higher in the DM + ALA + PIO group compared with non-treated DM group (70.2 ± 3.46 vs. 61.1 ± 2.91, P < 0.05) although significant differences were not present between combination therapy and monotherapy independent of ALA or PIO. Our results demonstrated that combination therapy using PIO based on ALA can give an additional benefit in peripheral nerve preservation in diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

The aim is to investigate whether there is a difference in CA 19-9 levels between diabetes and healthy subjects except malignancies and associated factors with CA 19-9 in diabetes. We performed a retrospective analysis in 146 type 2 diabetes and 154 healthy subjects who visited our medical institution from 2005 to 2009. We compared the CA 19-9 in each group, and analyzed clinical and biochemical variables in diabetes. The average value of CA 19-9 in diabetes was higher than that of healthy subjects significantly (14.1 vs 8.1 U/mL, p < 0.01). CA 19-9 had a positive correlation with HbA1c (r = 0.22), fasting plasma glucose (r = 0.24), and C-reactive protein (r = 0.38) in diabetes (p < 0.05). 48 type 2 diabetes who showed decreased CA 19-9 during follow-up of 1.8 ± 1.0 years were also improved in glucose control state. The proportion of insulin use for glucose control was significantly higher in the group of CA 19-9 ≥ 37 U/mL (75.0 %) as compared with the group of CA 19-9 < 37 U/mL (34.0 %). CA 19-9 was significantly higher in the patients with diabetic peripheral neuropathy (DPN) as compared with those without DPN (p = 0.02). However, after excluding the influences from glycemic control state, significant difference was not observed. Our results indicate not only that CA 19-9 is influenced by glycemic control state but also can be elevated irrespective of any malignancy in diabetes. Therefore, CA 19-9 should be interpreted carefully in diabetic patients when CA 19-9 is used as the tool for malignancy screening.

A 58-year-old male was brought to our emergency department because of acute onset of visual disturbances and headache. His past medical history revealed no specific illness. He was a nonsmoker. On history taking, we learned that the patient had experienced weight loss with decreased sexual activity for several months. On physical examination, beard and axillary hair were decreased. The thyroid gland was mildly enlarged on palpation. Examination of vital signs revealed a blood pressure of 120/60 mmHg, heart rate of 80/min, respiration rate of 18 breaths/min, and body temperature of 36.5 C. Radiologic examinations with brain computed tomography (CT) showed a mass in the pituitary gland. Laboratory tests revealed as follows: a serum sodium of 134 (135–150) mmol/L, serum glucose of 6.6 mmol/L, FSH of 0.9 (1.4–18.1) IU/L, LH of \0.07 (1.5–9.3) IU/L, testosterone of\0.01 (0.09–0.37) nmol/L, prolactin of 456.5 (78.3–691.3) pmol/L, IGF-1 of 9.0 (9.3–38.0) nmol/L, free T4 of 19.10 (11.5–22.7) pmol/L, TSH of \0.01 (0.55–4.78) mIU/L, and ACTH of 5.87 pmol/L. The random cortisol level was not measured before hydrocortisone was administered. Sellar magnetic resonance imaging (MRI) showed a 27 9 35 9 24 mm pituitary mass that was bulging into suprasellar area and contained a fluid–fluid level (Fig. 1a). Pituitary macroadenoma with hemorrhage was highly suspected. Standard ophthalmologic examination showed bilateral hemianopsia. Therefore, a high dose of hydrocortisone was administered intravenously immediately. However, neurosurgery was performed on this patient because of persistence of the visual field defect despite steroid treatment. Endonasal transsphenoidal surgery for pituitary adenoma was performed. The final pathologic diagnosis was pituitary adenoma originating from a gonadotrope. On the other hand, a diffuse goiter was detected on palpation and the free T4 level was in the high range of normal as described earlier. Therefore, we measured the free T3 level and thyroid autoantibody. Results revealed a free T3 of 9.7 (3.1–6.8) pmol/L, anti-TPO antibody of 600 (*34) IU/mL, and anti-TSH receptor antibody of 33.82 (*1.75) IU/L. Thyroid scan with pertechnetate revealed a diffuse toxic goiter that was compatible with primary hyperthyroidism (Fig. 1b). Therefore, antithyroid drug was started with physiologic replacement of hydrocortisone. Pituitary apoplexy is a life-threatening clinical syndrome characterized by sudden onset of headache, and visual impairment caused by the rapid enlargement of the pituitary adenoma usually due to hemorrhage. Various predisposing factors of pituitary apoplexy, such as systemic hypertension, alteration of intracranial pressure gradients, head trauma, pituitary irradiation, pregnancy, cerebral angiography, anticoagulation, dynamic study of pituitary gland, hemodialysis, and surgeries including cardiac surgery, have been reported. Among these factors, hypertension was the most common predisposing factor. It is also well known that thyroid dysfunction results in changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances [1]. Therefore, theoretically, it is possible that primary thyroid dysfunction causes pituitary apoplexy in patients with pituitary adenoma. However, clinically, the association between pituitary apoplexy and thyroid dysfunction has been unclear, and only one case of pituitary apoplexy caused by primary K. A. Lee T. S. Park H. S. Baek H. Y. Jin (&) Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Chonbuk National University, Geonji Road #20, Deokjin-gu, Jeonju 561-712, South Korea e-mail: mdjinhy@jbnu.ac.kr

Although fine needle aspiration (FNA) is an useful and accurate tool in the diagnosis of thyroid nodules with minimal side effect [1, 2], massive intrathyroidal hemorrhage causing acute airway compression is possible and can be fatal. Several cases causing emergent thyroidectomy due to acute airway compression after FNA have been reported [3, 4]. However, it is difficult to determine the necessity of thyroidectomy because intrathyroidal hemorrhage can be resolved via tight compression without thyroidectomy if the airway compression is not serious. Our experience is as follows: A 45-year-old woman visited emergency room due to painful anterior neck swelling and mild dyspnea after diagnostic FNA. After FNA, the patient did not complain of any specific symptoms on the FNA site; however, 3 h later, the patient felt painful swelling, mild dyspnea, and dysphagia in the anterior neck area without subcutaneous hematoma. At that time, there was no abnormal finding in the thyroid function and blood coagulation test. A flexible laryngoscopic examination did not show narrowing of the trachea, although sonography (Fig. 1a) and computed tomography scan revealed diffuse swelling of the bilateral thyroid lobes. Surgery was considered, but no definite active bleeding was observed in CT image. Therefore, the patient was closely observed with tight compression on the swelling site for several hours. Fortunately, the dyspnea and painful swelling were reduced over time. The patient underwent continuous tight compression around the neck using an elastic bandage for one day after manual compression. After 2 days, follow-up thyroid sonography (Fig. 1b) demonstrated findings similar to those before the FNA, with complete resolution of the intrathyroidal hemorrhage. The painful swelling of the neck had subsided, and the comfort level of the patient returned to the level before the FNA procedure. Thyroid nodules have plentiful and aberrant or weakened vessels, and FNA penetration of these vessels can cause bleeding around the aspirated nodule within the thyroid capsule [3–5]. Therefore, clinicians should be aware of the complications of FNA and perform the procedure carefully, and should check for hemorrhage or hematoma after the procedure. Acute intrathyroidal hemorrhage after FNA can lead to severe airway compression, and prompt intervention such as thyroidectomy is needed in the case of rapid progression with continuous active bleeding. At the same time, careful consideration before emergent thyroidectomy should be taken to determine whether spontaneous resolution is possible. In this regard, there are few reports which show completely resolved cases from serous intrathyroidal hemorrhage after FNA. In addition, there are few cases to help determine whether emergent thyroidectomy should be performed. Therefore, we would like to propose careful manual compression at the aspiration site and careful decision-making in performing emergent thyroidectomy according to the presence of airway compression and active bleeding. However, it is necessary to discuss the indication or guideline for decision about conservative management and thyroidectomy in the Y. S. Lee Radiology Department, Chonbuk National University Hospital, Jeonju, South Korea

The online version of the original article can be found under doi:10.1007/s12020-013-9947-5.S. h. Kim T. S. Park H. S. Baek H. Y. Jin (&)Division of Endocrinology and Metabolism, Departmentof Internal Medicine, Research Institute of Clinical Medicineof Chonbuk National University, Chonbuk National UniversityHospital, Chonbuk National University Medical School, 634-18,Keum-Am Dong, Jeonju 561-712, South Koreae-mail: mdjinhy@jbnu.ac.kr